Cytokines are a large family of more than 160 soluble intercellular signaling proteins involved in the regulation of the immune system. IL-17E (IL-25) belongs to a family of cytokines which possess homology to IL-17 (Aggarwal et al., (2002) J. Leukoc Biol 71: 1-8; and Hurst et al., (2002) J Immunol 169: 443-453). The interleukin 17 family of cytokines share a conserved cysteine-knot fold near the C-terminus. All interleukin 17 family members, except interleukin 17B, are disulfide-linked dimers. Interleukin 17E proteins from a variety of species share significant amino acid sequence identity. For example, mature human interleukin 17E shares 76% identity with mature mouse interleukin 17E. Various isoforms of human interleukin 17E which share significant homology have been identified (Kim et al., (2002) Blood 100: 2330-2340; Lee et al. (2001) J. Biol. Chem. 276:1660-1664 and Fort et al. (2001) Immunity 15:985-995).
Although IL-17E is structurally related to IL-17, its biological effects differ dramatically from those described for IL-17 and other IL-17 family cytokines. The expression of IL-17E in mice results in the expansion of eosinophils through the production of IL-5 from an unidentified non-T-cell population (Hurst et al., (2002) J Immunol 169: 443-453; Pan et al., (2001) J Immunol 167: 6559-6567; and Fort et al., (2001) Immunity 15: 985-995). In addition, IL-17E induces elevated gene expression of IL-4 and IL-13 in multiple tissues and the resultant T helper 2 (TH2)-type immune response which manifests as increased serum immunoglobulin E (IgE) levels and pathological changes in the lungs and digestive tract with eosinophilic infiltrates, increased mucus production, and epithelial cell hyperplasia (Hurst et al., (2002) J Immunol 169: 443-453; Pan et al., (2001) J Immunol 167: 6559-6567; and Fort et al., (2001) Immunity 15: 985-995), indicating that IL-17E is capable of amplifying inflammatory responses.
Although IL-17E mRNA was shown to be expressed in polarized TH2 cells (Fort et al., (2001) Immunity 15: 985-995), IL-17E mRNA was also detected in multiple tissues, including colon, uterus, stomach, small intestine, kidney and lung (Hurst et al., (2002) J Immunol 169: 443-453; Pan et al., (2001) J Immunol 167: 6559-6567; and Fort et al., (2001) Immunity 15: 985-995), suggesting that in addition to TH2 cells, other cell types may produce IL-17E. Bone marrow-derived mast cells are also capable of producing IL-17E upon IgE crosslinking, therefore, mast cell-derived IL-17E may be involved in the augmentation of TH2-type immune responses (Ikeda et al., (2003) Blood 101: 1341-1346).
The identification of polypeptides having sequence similarity to interleukin-17, including two isoforms of IL-17E, and their therapeutic use has been described. For example, U.S. Pat. Nos. 6,579,520, and 6,569,645, and U.S. patent Application Nos. 20040043397; 20030203451; 20030199044; 20030186306; 20030180255; 20030054442; 20030008815; 20030003546; 20020182673 and 20020177188 describe a family of polypeptides, including interleukin 17E, which have sequence identity with interleukin 17, as well as interleukin 17 receptors and the nucleic acid molecules encoding these polypeptides. The family of polypeptides are shown to stimulate T-cell proliferation/activation and it is, therefore, speculated that they may be useful as adjuvants to stimulate T cell proliferation/activation to tumour antigens and thereby promote an anti-tumour response. No experimental data, however, is provided to demonstrate the immunoadjuvant effect of these polypeptides.
In direct contrast to the teaching in above-noted patents and patent applications, U.S. Patent Application Nos. 20050074427; 20050048029; 20050003451; 20030124092; 20020037524 describe a potential role for interleukin 17-like polypeptides in progression of cancers such as lymphoma and suggest the use of antagonists to the interleukin 17-like polypeptides for the treatment of cancerous or lymphoma conditions.
U.S. Patent Application Nos. 20050064391; 20040241137; 20040126357; 20040091503; 20040180389; 20040151728; 20040170960; 20040142889; 20040126793 and 20040122217 describe lectin compositions and methods of using same for modulating an immune response to an antigen. The compositions comprise an antigen bearing target and a fusion polypeptide that comprises a first part which is capable of binding to a carbohydrate and a second part which is capable of binding to a cell. The second part of the fusion polypeptide is a ligand, such as a ligand for a cytokine receptor, CD40, an adhesion molecule, a defensin receptor, a heat shock protein receptor, a T cell costimulatory molecule, or a counterreceptor for a T cell costimulatory molecule. Exemplary ligands for cytokine receptors described in these applications include various interleukins, amongst which IL-25 is contemplated as an option. While the methods described in the applications include methods of modulating an immune response, treating a disease or reducing the number of metastases in a subject, these patent applications do not provide any experimental data demonstrating the anti-tumour activity of the described compositions.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.